The present invention relates to a method of treatment of bronchial and respiratory disorders with a therapeutic combination of a PDE4 inhibitor and a leukotriene antagonist. In particular, the present invention is directed to a method of treatment of bronchial and respiratory disorders with a therapeutic combination of ROFLUMILAST and SINGULAIR.
Cyclic nucleotide phosphodiesterase (PDE) inhibitors, particularly inhibitors of type IV (PDE4), are useful in the treatment of bronchial and respiratory disorders such as asthma and chronic obstuction pulminary disease (COPD). N-(3,5-dichloropyrid-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxybenzamide (ROFLUMILAST, BYK Gulden Lomberg Chemische Fabrik GmbH, Konstanz, Germany) is a PDE4 inhibitor described in U.S. Pat. No. 5,712,298.
Leukotriene antagonists, by a route different from PDE4 inhibitors, are also useful in the treatment of bronchial and respiratory disorders such as asthma and COPD. Montelukast, [R-(E)]-1-[[[1-[3-[2-(7-Chloro-2-quinolinyl)ethenyl]phenyl]-3-[2-(1-hydroxy-1-methylethyl)-phenyl]propyl]thio]methyl]cyclopropaneacetic acid, (SINGULAIR, Merck and Co., Inc, Rahway, N.J.) is a leukotriene antagonist described in U.S. Pat. No. 5,565,473. Other leukotriene antagonists are described in U.S. Pat. Nos. 4,649,157, 4,845,083, 5,028,615, and 5,244,899.
It would be desirable to provide a method that can take advantage of the different therapeutic pathways of a PDE4 inhibitor and of a leukotriene antagonist to more efficaciously treat asthma and COPD.
Bronchial and respiratory disorders are treated by the separate, sequential, or simultaneous administration of i) an amount of N-(3,5-dichloropyrid-4-yl)-cyclopropylmethoxy-4-difluoromethoxybenzamide, the pyridyl N-oxide thereof, or a pharmaceutically acceptable salt of either compound; and ii) an amount of a leukotriene antagonist, wherein the sum of the first and second amounts is a therapeutically effective amount.